Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2016 Oct 17;16(1):34.
doi: 10.1186/s40644-016-0092-2.

Effects of capecitabine treatment on the uptake of thymidine analogs using exploratory PET imaging agents: 18F-FAU, 18F-FMAU, and 18F-FLT

Christopher I McHugh  1 , Jawana M Lawhorn-Crews  2 , Dipenkumar Modi  2 , Kirk A Douglas  2 , Steven K Jones  1 , Thomas J Mangner  3 , Jerry M Collins  4 , Anthony F Shields  5
Affiliations

Effects of capecitabine treatment on the uptake of thymidine analogs using exploratory PET imaging agents: 18F-FAU, 18F-FMAU, and 18F-FLT

Christopher I McHugh et al. Cancer Imaging. .

Abstract

Background: A principal goal for the use of positron emission tomography (PET) in oncology is for real-time evaluation of tumor response to chemotherapy. Given that many contemporary anti-neoplastic agents function by impairing cellular proliferation, it is of interest to develop imaging modalities to monitor these pathways. Here we examined the effect of capecitabine on the uptake of thymidine analogs used with PET: 3'-deoxy-3'-[18F]fluorothymidine (18F-FLT), 1-(2'-deoxy-2'-[18F]fluoro-β-D-arabinofuranosyl) thymidine (18F-FMAU), and 1-(2'-deoxy-2'-[18F]fluoro-β-D-arabinofuranosyl) uracil (18F-FAU) in patients with advanced cancer.

Methods: Fifteen patients were imaged, five with each imaging agent. Patients had been previously diagnosed with breast, colorectal, gastric, and esophageal cancers and had not received therapy for at least 4 weeks prior to the first scan, and had not been treated with any prior fluoropyrimidines. Subjects were imaged within a week before the start of capecitabine and on the second day of treatment, after the third dose of capecitabine. Tracer uptake was quantified by mean standard uptake value (SUVmean) and using kinetic analysis.

Results: Patients imaged with 18F-FLT showed variable changes in retention and two patients exhibited an increase in SUVmean of 172.3 and 89.9 %, while the other patients had changes ranging from +19.4 to -25.4 %. The average change in 18F-FMAU retention was 0.2 % (range -24.4 to 23.1) and 18F-FAU was -10.2 % (range -40.3 to 19.2). Observed changes correlated strongly with SUVmax but not kinetic measurements.

Conclusions: This pilot study demonstrates that patients treated with capecitabine can produce a marked increase in 18F-FLT retention in some patients, which will require further study to determine if this flare is predictive of therapeutic response. 18F-FAU and 18F-FMAU showed little change, on average, after treatment.

Keywords: Capecitabine; FAU; FLT; FMAU; Oncology; PET.

PubMed Disclaimer

Figures

Fig. 1
Fig. 1
Tumor 18F-FLT Uptake in Patient 3. Axial (top) and coronal (bottom) 18F-FLT Images of a mediastinal metastasis (arrow) in a patient with esophageal cancer at baseline (a) and after 1 day of capecitabine therapy (b). Tumor SUVmean increased from 4.70 to 12.80
Fig. 2
Fig. 2
Tumor 18F-FMAU Uptake in Patient 7. Axial (top) and coronal (bottom) 18F-FMAU Images of a lung metastasis (arrow) in a patient with breast cancer at baseline (a) and after 1 day of capecitabine therapy (b). Tumor SUVmean increased from 3.76 to 4.63
Fig. 3
Fig. 3
Tumor 18F-FAU Uptake in Patient 15. Axial (top) and coronal (bottom) 18F-FAU Images of a tumor of the gastroesophageal junction (arrow) at baseline (a) and after 1 day of capecitabine therapy (b). Tumor SUVmean decreased from 3.47 to 2.07
See this image and copyright information in PMC

References

    1. Koukourakis GV, Kouloulias V, Koukourakis MJ, Zacharias GA, Zabatis H, Kouvaris J. Efficacy of the oral fluorouracil pro-drug capecitabine in cancer treatment: a review. Molecules. 2008;13:1897–922. doi: 10.3390/molecules13081897. - DOI - PMC - PubMed
    1. Simplicio AL, Clancy JM, Gilmer JF. Prodrugs for amines. Molecules. 2008;13:519–47. doi: 10.3390/molecules13030519. - DOI - PMC - PubMed
    1. Budman DR, Meropol NJ, Reigner B, Creaven PJ, Lichtman SM, Berghorn E, Behr J, Gordon RJ, Osterwalder B, Griffin T. Preliminary studies of a novel oral fluoropyrimidine carbamate: capecitabine. J Clin Oncol. 1998;16:1795–802. - PubMed
    1. Miwa M, Ura M, Nishida M, Sawada N, Ishikawa T, Mori K, Shimma N, Umeda I, Ishitsuka H. Design of a novel oral fluoropyrimidine carbamate, capecitabine, which generates 5-fluorouracil selectively in tumours by enzymes concentrated in human liver and cancer tissue. Eur J Cancer. 1998;34:1274–81. doi: 10.1016/S0959-8049(98)00058-6. - DOI - PubMed
    1. Schuetz JD, Wallace HJ, Diasio RB. 5-Fluorouracil incorporation into DNA of CF-1 mouse bone marrow cells as a possible mechanism of toxicity. Cancer Res. 1984;44:1358–63. - PubMed

MeSH terms

LinkOut - more resources